Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats.

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for ß-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Thyroxine increases Serca2 and Ryr2 gene expression in heart failure rats with euthyroid sick syndrome

ABSTRACT Objective The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups. One group (9 Wistar rats) with HF received 1.0 µg of T4/100 g of body weight for five consecutive days (HFS/T4); the other group (9 Wistar rats) received isotonic saline solution (HFS/S). The animals were sacrificed after this treatment and examined for signs of HF. Samples from the left ventricles of these animals were analyzed by RT-qPCR for the expression of Serca2 and Ryr2 genes. Results Rats with HF developed euthyroid sick syndrome (ESS) and treatment with T4 restored the T3 values to the Sham level and increased Serca2 and Ryr2 gene expression, thereby demonstrating a possible benefit of T4 treatment for heart function in ESS associated with HF. Conclusion The T4 treatment can potentially normalize the levels of T3 as well elevated Serca2 and Ryr2 gene expression in the myocardium in heart failure rats with euthyroid sick syndrome.

Thyroxine increases Serca2 and Ryr2 gene expression in heart failure rats with euthyroid sick syndrome.

OBJECTIVE: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. MATERIALS AND METHODS: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups. One group (9 Wistar rats) with HF received 1.0 µg of T4/100 g of body weight for five consecutive days (HFS/T4); the other group (9 Wistar rats) received isotonic saline solution (HFS/S). The animals were sacrificed after this treatment and examined for signs of HF. Samples from the left ventricles of these animals were analyzed by RT-qPCR for the expression of Serca2 and Ryr2 genes. RESULTS: Rats with HF developed euthyroid sick syndrome (ESS) and treatment with T4 restored the T3 values to the Sham level and increased Serca2 and Ryr2 gene expression, thereby demonstrating a possible benefit of T4 treatment for heart function in ESS associated with HF. CONCLUSION: The T4 treatment can potentially normalize the levels of T3 as well elevated Serca2 and Ryr2 gene expression in the myocardium in heart failure rats with euthyroid sick syndrome.

Polychlorinated biphenyls and thyroid hormones in adults: a systematic review appraisal of epidemiological studies.

Reported evidence regarding relationships between polychlorinated biphenyls (PCBs) and thyroid homeostasis in adults has been considered contradictory. The objective of this systematic review is to determine a possible association between PCB exposure and the circulating thyroid hormones and thyrotropin (TSH) levels in adults, by analyzing the quality of published studies. A systematic review of epidemiological papers was conducted using PubMed. An evaluation of the quality of 22 studies was performed, and the papers were classified into two tiers: Tier I for studies with higher quality scores (eight) and Tier II for studies with lower quality scores (14). It appears that PCBs can interfere with thyroid hormone homeostasis; however epidemiological evidence is not entirely clear. For triiodothyronine (T3) and thyroxine (T4), Tier I studies showed either an inverse (four cases for T3; five cases for T4) or no significant association (two cases for T3; five cases for T4) with PCBs. In the case of free thyroxine and TSH, the Tier I papers observed no clear association with PCB levels. Rigorous study design, assessment of potential confounding factors, and fuller reporting of methods and results in future studies will facilitate understanding of whether PCB exposure is associated with changes in thyroid function.

Effect of conjugated equine estrogens and tamoxifen administration on thyroid gland histomorphology of the rat.

OBJECTIVE: The aim of this study was to evaluate the action of the conjugated equine estrogens and tamoxifen on the morphology of thyroid gland in ovariectomized (OVx) rats. METHODS: Conjugated equine estrogens (CEE), clinically used as estrogen therapy, is a complex formulation containing multiple estrogens that decrease menopausal symptoms. Thirty ovariectomized rats were randomly divided into 3 treatment groups: GI, vehicle (propylene glycol); GII, CEE 200 microg/kg per day; and GIII, tamoxifen 1 mg/kg per day. Another group of 10 rats with intact ovaries (GIV) was included, treated with the vehicle, and sacrificed during estrous. All animals were treated by gavage for 50 days, after which they were sacrificed. Blood samples were collected, and the thyroid was removed for morphological analysis and PCNA evaluation through immunohistochemical study. RESULTS: The thyroid follicular cell height was increased in animals treated with CEE (14.90 +/- 0.20 microm), with TAM (14.90 +/- 0.10 microm), and in rats with intact ovaries (15.10 +/- 0.50 microm) in comparison to that of the vehicle group (9.90 +/- 0.20 microm) (P < 0.001). The follicular area was larger in the CEE (2,225 +/- 51 microm2) and TAM (2,127 +/- 67 microm2) groups compared to that of the vehicle group (5,016 +/- 53 microm2). The levels of T4 and T3 in rats treated with CEE, with Tamoxifen and in rats with intact ovaries, were higher than those those in the vehicle group (P < 0.001). The PCNA index in the vehicle group was lower than in other groups. CONCLUSION: Our data suggest that estrogen and tamoxifen administration has a proliferative effect on the thyroid.

Effect of conjugated equine estrogens and tamoxifen administration on thyroid gland histomorphology of the rat

OBJETIVO: Avaliar a ação dos estrogênios conjugados eqüinos e do tamoxifeno na histomorfologia da tireóide de ratas. MÉTODO: Estrogênios conjugados eqüinos são ministrados clinicamente como terapia estrogênica e contêm formulação complexa com muitos tipos de estrogênios que diminuem os sintomas da pós-menopausa. Trinta ratas adultas ooforectomizadas foram divididas aleatoriamente em três grupos: GI – veículo (propilenoglicol); GII - ECE 200 µg/Kg por dia; e GIII – TAM 1 mg/Kg por dia. Acrescentou-se ainda um grupo de 10 animais com os ovários intactos e tratados com veículo (GIV). Todos os animais foram tratados por gavagem durante 50 dias consecutivos, ao final foram coletadas amostras do sangue e a tireóide removida e processada para análise morfológica e imunohistoquímico para avaliar o PCNA. RESULTADOS: A maior altura das células foliculares foi observada nos animais tratados com ECE (14,90 ± 0,20 µm), TAM (14,90 ± 0,10 µm) e no grupo com ovários intactos (15,10 ± 0,50 µm), comparando-se aos controles ovariectomizados (GI) (9,90 ± 0,20 µm) (p<0,001). A maior área folicular foi detectada nos grupos tratados com ECE (2.225 ± 51 µm2) e com TAM (2.127 ± 67 µm2), comparado ao veículo (5.016 ± 53 µm2) em animais ooforectomizados. Os níveis de T4 e T3 nos grupos tratados com ECE, com TAM e no grupo com ovários intactos foram maiores do que no grupo tratado com veículo (p<0,001). O índice do PCNA no grupo tratado com veículo foi menor do que em todos os outros grupos. CONCLUSÃO: Nossos dados sugerem que a administração de ECE e TAM resulta em atividade proliferativa na tireóide.

Effect of grazing pasture with a low selenium content on the concentrations of triiodothyronine and thyroxine in serum, and GSH-Px activity in erythrocytes in cows in Chile.

AIM: To determine the effect of grazing pasture that had a low selenium (Se) concentration on serum concentrations of triiodothyronine (T3) and thyroxine (T4), and erythrocyte glutathione peroxidase (GSH-Px) activity in dairy cows. METHODS: Forty pregnant Friesian cows were grazed on pasture that contained 0.03-0.04 ppm Se on a dry matter (DM) basis. Two months before parturition, 20 cows were randomly selected and treated with 1 mg Se/kg bodyweight subcutaneously, as barium selenate (Group Se-S). The other group (Se-D) was not supplemented. Blood samples were taken before supplementation (-60 days) and 30, 60, 90, 180 and 270 days after parturition, for determination of concentrations of T3 and T4 in serum, and GSH-Px activity in erythrocytes. RESULTS: Erythrocyte GSH-Px activity in the Se-D group was <60 U/g haemoglobin (Hb) throughout the experiment. Supplementation increased (p<0.05) activities to >130 U/g Hb throughout lactation. Mean serum concentrations of T4 in Se-D and Se-S cows increased from 23.7 (SEM 0.7) and 23.4 (SEM 0.8) nmol/L, respectively, in the prepartum period to 69.6 (SEM 0.1) and 67.6 (SEM 0.2) nmol/L, respectively, at 180 days of lactation (p<0.01), and no effect of Se supplementation was evident. Serum concentrations of T3 in Se-D cows decreased (p<0.05) from 1.6 (SEM 0.1) nmol/L prepartum to 1.0 (SEM 0.2) nmol/L at the beginning of lactation, and remained lower (p<0.05) than those in the Se-S cows which did not decrease after calving and ranged from 1.9 (SEM 0.1) to 2.4 (SEM 0.2) nmol/L throughout lactation. CONCLUSIONS: Serum T3 concentrations decreased during early lactation in unsupplemented cows grazing pastures low in Se (0.03-0.04 ppm) and both serum T3 and erythrocyte GSHPx activities were consistently lower throughout lactation compared with Se-supplemented cows. Se supplementation had no effect on serum T4 concentrations.

Alterations of the rat thyroid gland under experimental conditions

The thiyroid gland of rats, was studied under experimental conditions porvided by administration of several doses of lithium carbonate. It was noted a drug a cumulative effcct on the serum; and the decrease of T3 and T4 hormones in the blood, as well as, the red blood cells, hemoglobin, hematocrit platelets and leukocytes; the diameter of the thy roid follicles, the size of the follicular cells and colloid droplets. On the othcr hand the stroma was invaded by of collagen fibers and blood capillaries.